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Clostridium difficile infection (CDI) has become a global health challenge, due to the dramatic worldwide increase in incidence and severity in the past three decades. Furthermore, the incidence of CDI has increased in surgical patients. The surgery itself is a known risk factor, that, together with the postoperative care (hospitalization, antibiotic treatment, intensive care unit admission), facilitate the development of CDI. Therefore, a matter of paramount importance is the optimization of the management of surgical patients and prevention of Clostridium difficile infection.